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Requirements for Submission and Approval for the use of Recombinant DNA

Columbia University Institutional Biosafety Committee Policy/Operating Procedures (Charge)

Recombinant DNA use is inseparable from research progress in the life sciences and other fields.  Many of the same hazards associated with standard microbiological activities carry over into this field based on the use of potentially infectious vectors and genetic materials from recognized pathogens.  The University seeks to address and mitigate these hazards through the appropriate application of biological safety processes and adherence to relevant regulatory mandates.

Introduction
Recombinant DNA refers to either: (i) molecules constructed outside of living cells by joining natural or synthetic DNA segments to DNA molecule that can replicate in a living cell, or (ii) molecules that result from the replication of those described in (i) above.

The University’s Institutional Biosafety Committee (IBC) is charged with facilitating compliance with the NIH’s Guidelines for Research Involving Recombinant DNA Molecules .  The “Guidelines” are actually requirements and the failure to adhere to them may result in suspension of NIH funding to an individual PI or the entire institution.  The Guidelines apply to all recombinant DNA ( rDNA) activities at an institution where any work with recombinant DNA receives NIH funding.  Stated another way, the Guidelines apply to all rDNA work at Columbia regardless of the individual project’s funding source. See also Investigator responsibilities under the NIH guidelines” brochure.

Responsibilities

  • Recombinant DNA Activities Committee (RAC)  group within the NIH is responsible for carrying out the functions specified in the NIH Guidelines, as well as others specified in its charter or assigned by the Secretary of Health and Human Services or the NIH Director. 
  • Office of Biotechnology Activities (OBA)  serves as a focal point for information on recombinant DNA activities and provides advice within and outside NIH including institutions, Biological Safety Officers, Principal Investigators, Federal agencies, state and local governments, and the private sector.
  • Columbia University’s Institutional Biosafety Committee (IBC)  is responsible for facilitating compliance with the Guidelines through activities that include education and training, review of rDNA proposals, and periodic reporting to the NIH as required by the Guidelines.
  • Principal Investigators and laboratory staff are responsible for submitting their rDNA proposals to the IBC in a timely manner, adherence to the biological safety practices appropriate to the risk of their research materials, and seeking IBC assistance on any safety or compliance issues related to their work with rDNA or other biological materials.
  • Columbia University Environmental Health & Safety (EHS) provides technical support to the IBC and has primary role in development and implementation of research safety policies.

Approval of rDNA Activities
The Guidelines specify different levels of approval and registration requirements (Sections III-A through Section III-F) that must be met prior to or upon initiation of work.  Certain uses of rDNA (Section III-F) are exempt from any approval or registration requirements.

Section III-A:  Experiments that Require Institutional Biosafety Committee Approval (IBC), RAC Review, and NIH Director Approval Before Initiation.

The deliberate transfer of a drug resistance trait to microorganisms that are not known to acquire the trait naturally if such acquisition could compromise the use of the drug to control disease agents in humans, veterinary medicine, or agriculture.

Section III-B :  Experiments That Require NIH/OBA and IBC Approval Before Initiation.

Experiments Involving the Cloning of Toxin Molecules with LD50 < 100 nanograms per kilogram body weight.

Section III-C :  Experiments that Require IBC and Institutional Review Board Approvals and RAC Review Before Research Participant Enrollment. 

Deliberate transfer of recombinant DNA, into one or more human research participants(eg: a clinical trial); Institutional Review Board (IRB) approval is also required.

Section III-D:  Experiments that Require IBC Approval before Initiation

  • Use of Risk Group 2, 3, 4 or Restricted Agents as host-vector systems (ex. lentiviral or adenoviral vectors)
  • Cloning of DNA from Risk Group 2 or higher agents into non-pathogenic prokaryotic or lower eukaryotic host-vector systems
  • Use of infectious viruses or defective viruses in the presence of helper virus in tissue culture
  • Experiments involving transgenic or non-transgenic animals administered rDNA (does not include generation or breeding transgenic rodents, see Section III-E)
  • Experiments involving more than 10 liters of culture
  • Experiments involving high risk Influenza Viruses

Section III-E:  Experiments that Require IBC Notice Simultaneous with Initiation

  • Formation of recombinant DNA molecules containing no more than 2/3’s of the genome of any eukaryotic virus if it is demonstrated that the cells lack helper virus for the specific Families of defective viruses being used
  • Generation or interstrain breeding where one or both of the strains is transgenic if the experiment requires BL1 containment; experiments that require higher levels of containment are covered under Section III-D,  IBC approval required before initiation.  Note: propagation of a single transgenic strain is exempt.

Section III-F: Exempt Experiments 
Those that are not in organisms or viruses

  • Those that consist entirely of DNA segments from a single nonchromosomal or viral DNA source, though one or more of the segments may be a synthetic equivalent.
  • Those that consist entirely of DNA from a prokaryotic host including its indigenous plasmids or viruses when propagated only in that host (or a closely related strain of the same species), or when transferred to another host by well established physiological means.
  • Recombinant DNA molecules that consist entirely of DNA segments from different species that exchange DNA by known physiological processes, though one or more of the segments may be a synthetic equivalent.  (see Appendix A of the NIH Guidelines).
  • Recombinant DNA molecules containing less than one-half of any eukaryotic viral genome that are propagated and mainta ined in cells in tissue culture.
  • Escherichia coli K-12, Saccharomyces, Bacillus subtilis or Bacillus licheniformis Host-Vector Systems . 
  • Propagation of a single transgenic strain is exempt.    

The NIH provides additional guidance for the use of rDNA in animals, including transgenics.

Submitting Your Recombinant DNA Application

  • Go https://www.rascal.columbia.edu.
  • Select ‘Hazardous Materials’ from the menu on the left side of the welcome screen.
  • Log in with your CU UNI and password.
  • Select “Recombinant DNA (Appendix A)”:
    • For activities that will NOT involve the administration of recombinant DNA to vertebrate animals, select “Invitro/Invertebrates only ”.  Once the Appendix is saved, it can be directly submitted to the IBC.
    • For activities that will involve the administration of recombinant DNA to vertebrate animals, or the generation or breeding of transgenic animals select “Invitro/Invertebrates only” which then must be attached to the pertinent IACUC protocol.
    • For activities requiring BSL-2/ABSL-2 containment or greater, the submission of an Appendix B to describe the use of infectious materials is also required.
    • For human gene transfer protocols complete and sign form “Application for the use of Recombinant DNA (rDNA) Molecules in Human Gene Transfer” and follow the submission instructions on the form. If RAC Assessment is requested also complete this form: "RAC Assessment  Determination- IBC Application Addendum".

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